Mechanistic studies of carcinogenesis indicate an important role
of endogenous oxidative damage to DNA that is balanced by elaborate
defense and repair processes. Also key is the rate of cell
division, which is influenced by hormones, growth, cytotoxicity,
and inflammation, as this determines the probability of converting
DNA lesions to mutations. These mechanisms underlie many
epidemiologic observations. Epidemiological evidence indicates that
avoidance of smoking, increased consumption of fruits and
vegetables, and control of infections will have a major effect on
reducing rates of cancer. A substantial reduction in breast cancer
is likely to require modification of sex hormone levels, and
development of practical methods for doing so is a high research
priority. Animal cancer tests are usually done on synthetic
chemicals at the maximum tolerated dose (MTD) of the chemical.
These results are being misinterpreted to mean that low doses of
synthetic chemicals and industrial pollutants are relevant to human
cancer. About half of the chemicals tested, whether
synthetic or natural, are carcinogenic to rats or mice at these
high doses. A plausible explanation for the high proportion of
positive results is that testing at the MTD frequently can cause
chronic cell killing and consequent cell replacement, which is a
risk factor for cancer that can be limited to high doses.